Ion channels under the sun.

Abstract

The FASEB Journal • Essay Ion Channels under the Sun Geoffrey W. Abbott* ,1 and Geoffrey S. Pitt † *Bioelectricity Laboratory, Departments of Pharmacology and Physiology and Biophysics, School of Medicine, University of California, Irvine, California, USA; and † Departments of Medicine/ Cardiology and Pharmacology, Duke University Medical Center, Durham, North Carolina, USA In late june 2013, scientists from all corners of the globe gathered in Nassau, Bahamas, for the Sixth Biennial FASEB Science Research Conference (SRC) on Ion Channel Regulation. Afternoons were spent enjoying snorkeling, diving, sailing, or relaxing amid palm trees swayed by the gentle trade winds; mornings and evenings were all business, as the latest research in the burgeoning field of ion channel regulation was debated. Ion-conducting proteins are thought to account for 1% of human genes, are essential for the function of all living cells and for electrical activity in living organisms, and underlie such diverse processes as fluid homeosta- sis, volume regulation, muscular contraction, nervous signaling, gastric acidification, and endocrine function. Although ion channels have historically been under- represented as therapeutic targets, ion channel dys- regulation is a key feature in some of the most pervasive threats to 21st century public health, including diabetes and other metabolic disorders, and neurodegenerative diseases. In an era in which the study of membrane proteins is arguably defined and dominated by atomic-level in- sights into structure and the molecular correlates of function, regulatory processes might, at first, seem a side-note not worthy of an entire conference. However, as the speakers and attendees at the FASEB SRC on Ion Channel Regulation demonstrated, nothing could be further from the truth. High-resolution, structural stud- ies have afforded us an unprecedented understanding of how ion channels and transporters operate, answer- ing some long-standing questions and fleshing out hypotheses and theories generated by earlier functional studies. Yet, in an era when our tools allow us to address the biomedical relevance and translational ramifica- tions of basic research, as physiologists and channelolo- gists, we are, more than ever before, seeking to discover how ion channels function in native systems and how they misbehave with consequences for human health. As physiologists, we have historically always broken things to help understand how they work. This natu- rally yields information as to what happens in ion channelopathies (diseases involving disruption of ion channel function) and consequent therapeutic op- tions. When Hodgkin and Huxley (1) analyzed sodium and potassium ion fluxes in the squid giant axon, eliminating the sodium influx by removing external bath sodium, as they pieced together the ionic ele- 0892-6638/14/0028-1957 © FASEB FASEB SRC on Ion Channel Regulation, June 23–28, 2013, Nassau, Bahamas. Conference logo, depicting an ion channel selectivity filter in the form of twin coconut palms (designed by G. W. Abbott). Image Copyright Federation of American Societies for Experimental Biology. ments of action potentials, they set the groundwork for manipulation of ionic currents to stem abnormal elec- trical activity to prevent or treat disorders, including epilepsy and chronic pain. Their work inspired use of pharmacologic agents to inhibit specific sodium or potassium channels to probe their contribution to the axonal action potential (2, 3), experiments that mir- rored what is now known to occur unintentionally in drug-induced cardiac arrhythmias, in which drug-in- duced ion channel blockade predisposes to life-threat- ening ventricular arrhythmias (4). Similarly, any scien- Correspondence: 360 Medical Surge II, Dept. of Pharma- cology, School of Medicine, University of California, Irvine, CA 92697, USA. E-mail: abbottg@uci.edu doi: 10.1096/fj.14-0501ufm